Burden of Aging: Health Outcomes Among Adolescents and Young Adults With Sickle Cell Disease

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were summarized to reflect the total number of barriers experienced in the past 12 months.
Psychosocial factors were measured by the National Institutes of Health resource HealthMeasures, which includes 4 validated health-related quality of life measurement systems. 12 The systems used in this study were the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), 13 Quality of Life in Neurological Disorders (Neuro-QoL), 14 and Patient-Reported Outcomes Measurement Information System (PROMIS). 15 Item responses for the ASCQ-Me and Neuro-QOL outcomes were uploaded to the HealthMeasures Scoring Service, where T-scores were generated. The ASCQ-Me 13 assessed sleep impact and reliance on others. Higher T-scores indicated more desirable outcomes (ie, better sleep and less reliance on others). 13 The Neuro-QOL 14 assessed cognitive functioning and task management. Higher T-scores indicated more desirable outcomes (ie, better cognitive function and better task management). 14 Depression was measured using the 4-item PROMIS 15 short form for Emotional Distress-Depression. Higher T-scores indicated less desirable outcomes (ie, more severe depression).
The aim was to identify differences in 10 health-related outcomes between adolescents and YAs. Univariate models examined the relationships between each outcome and the covariates. All covariates statistically significant at P < 0.1 were included as candidate variables for the final multivariable models. To prevent collinearity, variables significantly correlated with age group, the primary covariate of interest, were not included in the model. Backward elimination, using a significance cutoff of 0.05, was used to identify the best fitting models, and age group was included in each multivariable model, regardless of significance. Analyses were conducted in SAS Version 9.4 (SAS Institute Inc., Cary, NC).
A total of 996 SCDIC registry participants met inclusion criteria. Baseline characteristics of the adolescents (n = 214; 21.5%) and YAs (n = 782; 78.5%) are presented in Table 1. YAs were more likely to be high school graduates, employed, receive regular blood transfusions, have severe pain, have pain so bad that it was hard to finish tasks, less likely to see a SCD specialist or hematologist for most of their care, and more likely to have taken hydroxyurea compared with adolescents.
At the time of study enrollment, 51.9% of YAs and 30.4% of adolescents had experienced at least 1 event of organ dysfunction (Table 1). YAs having a severe SCD genotype, receiving regular blood transfusions, and higher pain frequency were associated with more dysfunctional organs (Table 2). Compared with adolescents, YAs experienced significantly more avascular necrosis, stroke, pulmonary hypertension, retinopathy, and chronic pain (Suppl. Table S1).
The mean number of acute visits over the past 12 months was 5.0 (±8.8) for YAs and 2.2 (±2.6) for adolescents (Table 1). YAs and those with prior use of hydroxyurea had significantly more acute visits over the past 12 months ( Table 2). The mean number of barriers to medical care was 0.6 (±1.3) among YAs and 0.1 (±0.4) among adolescents (Table 1). YAs and females experienced more barriers to medical care ( Table 2).
The mean depression t-score was 46.1 (±8.1) among YAs and 43.7 (±7.0) among adolescents (Table 1). YAs and those with more frequent pain were associated with higher self-reported depression ( Table 2). As reported by participants, 79.0% of YAs and 87.1% of adolescents had never received treatment for depression (Table 1). Current depression treatment was significantly associated with females, Hispanic ethnicity, and pain frequency ( Table 2). Age group was not significantly associated with current depression treatment. According to the medical record, 19.4% of YAs and 10.8% of adolescents had record of anxiety (Table 1). Anxiety was significantly associated with regular blood transfusions and prior use of hydroxyurea (Table 2). Age was borderline significantly associated with anxiety.
AYAs with SCD are a vulnerable population due to the increasing SCD severity. As hypothesized, the current study found that YAs with SCD experience more dysfunctional organs, increased acute visits, increased medical barriers, depression, and poorer sleep compared with adolescents with SCD. On the contrary, YAs reported higher cognitive function and task management than adolescents.
It is well known that the frequency of acute events and SCD-related mortality increases as patients age. 2,[16][17][18] The current study expanded prior work demonstrating that YAs were more likely to experience dysfunctional organs and mental health complications than adolescents, supporting and possibly explaining the rising mortality rates in young adulthood. Transition programs must anticipate the increased frequency of clinical outcomes (ie, increased disease burden) that starts in adolescence and into adulthood, thus preparing emerging adults to remain vigilant and aware of their progressive symptoms. We found that YAs were more likely to be treated with hydroxyurea, contrasting with a previous study where only 37% of YAs with SCD were prescribed hydroxyurea and prescription fills decreased as individuals aged. 19 This difference is likely attributable to differences in study design, as population-level data that included community clinics may reflect lower access to disease-modifying therapies than our current study, which primarily comprises academic institutions. 20 Previous research has found that among AYA with SCD, patients with elevated distress/depression reported significantly higher pain frequency than those with minimal distress/ depression. 21,22 Poor sleep has also been linked to worsened depression. 22,23 The current study confirmed these associations between pain frequency, depression, and sleep. Although the current study found that YAs have an increased prevalence of depression, there was no difference in the treatment of depression between adolescents and YAs. This demonstrates the importance of allocating mental health resources during healthcare transitions to monitor AYAs and provide interventions to prevent added distress from life changes.
Although the adjusted association between age and anxiety was insignificant, it is important to consider how anxiety might increase during transition. During transition, AYAs often shift to an unfamiliar care environment 6 and face financial/insurance and time-constraint barriers. The current study showed that YAs face more barriers to receiving medical care than adolescents and are less likely to receive care from an SCD specialist. Addressing anxiety and barriers to care throughout transition is important.
Strengths of this study include that it is a large sample of SCD AYA, providing sufficient power to detect age differences. Limitations of this study include that some outcomes are reported at enrollment, where participants are asked to recall events in the past year, which may introduce recall bias. Additionally, individuals potentially sought care at facilities other than the included sites; therefore, health care utilization may not be completely ascertained. Finally, the nature of the study limits our ability to explore any of causal association between outcomes and covariates.
As individuals with SCD transition to adulthood, it is crucial to anticipate the increased severity of health outcomes and have heightened attention to mental health. This study provides evidence to inform future guideline development, research investigation, and health services planning. Specifically, the AYA period requires interventions, such as (1) allocating resources toward mental health services, (2) addressing anxieties and barriers with transition programming, (3) building self-management skills to ensure patients remain engaged with their care, and (4) addressing the high frequency of pain interference and severity in YAs. These interventions must be implemented as an integral part of transition programming and continued throughout adult care.